1. Field of the Invention
This invention relates to preparative chromatography columns, i.e., chromatography columns in which molecular species are extracted from source solutions in high amounts for commercial use rather than for analytical purposes.
2. Description of the Prior Art
The chromatography columns to which the present invention is primarily directed are preparative chromatography columns designed for plug flow of a mobile phase through a packed bed of solid or semi-solid stationary phase made from soft (semi-solid) or rigid (solid) particles. The typical such column is a cylinder closed at each end by plates, each plate equipped with a fluid port, a distribution system, and a filter. The cylinder is uniformly filled with a separation medium or media, packed to form a “bed.” The filters have pore sizes that are smaller than the particle size of the media to retain the media within the cylinder, and yet large enough to allow the process liquids (i.e., the mobile phase) to pass through the filters and hence the column. The distribution system ensures that the process liquid is spread across the full width of the bed, thereby making maximal use of the bed.
The typical preparative chromatography column is large enough in diameter that separation within the column can be performed at a commercially useful throughput rate, i.e., one that will produce the extracted species at an economically viable production rate. The typical column is also small enough in depth that the pressure drop through the column is low, thereby avoiding the need for a high pump pressure to force the mobile phase through the column. There must be sufficient depth however to provide the mobile phase with a residence time that is long enough to allow proper interaction between the mobile and stationary phases. The typical column also contains a plunger or piston head that is lowered to contact and compress the stationary phase to a desired height. In operation, the mobile phase enters the column at the top through the plunger which includes a distributor plate to spread the mobile phase across the full width of the bed, thereby making maximal use of the bed.
The performance of a preparative chromatography column of the type described above is very sensitive to the degree of uniformity of the stationary phase. Optimal operation is achieved when the bed is homogeneous, compact, and of uniform depth such that the mobile phase is evenly distributed across the width of the bed. In the present state of art, the need for a stationary phase that is adjustable yet stable during purification, sanitization, storage and transportation of the column has led to columns with adjustable mechanical assemblies. Sealing between parts of the column, especially between the plunger and the column tube or between the bottom plate and the tube, requires tight adjustment of the parts, close alignment of the parts, and a smooth interior surface of the column tube. In addition, particularly in columns that are used for purifying food or drugs, the parts of the column that are in contact with the product, including the tube itself, the plates, and the distributors, must be made of special materials that are stable and inert, i.e., that neither leach into the product nor corrode upon contact with the product. As a consequence, the number of column parts, the volume of the column, the materials from which the parts are made, and the dimensional precision of the parts, make the column expensive and thus not suitable for single-use applications. The use of other forms of media, such as membranes or monoliths, could be simpler and less expensive but often fail to provide the same degree of purification.
The transportation of packed columns on long distances, for instance with the pre-packed or disposable columns applications, is also a challenge for maintaining the performance of the column. All the packing methods which only use downwards strengths, such as flow circulation and axial compression for column packing, succeed to settle the media particles in some kind of equilibrium after a short or long period, where each particle finds support on the lower particles. But this arrangement might not be optimal: excessive voids can still take place due to the friction of the tube walls, or due to the difference in size and shape of particles. The random stacking of these particles is also not optimal: the vibration, shocks and tilting and thermal variations during the transportation often induce local re-arrangements of the particles resulting with further compression of the bed, forming of supernatant, initiation of bed cracking. This prevents the transportation of packed columns on long distances, especially when non compressible chromatography media is used, where the bed is not maintained under compression.